In general, the active ingredients of medicinal compositions for oral administration are required, for example, to be excellent in terms of solubility, stability, and peroral absorbability and be produced by a method capable of mass production. In the case of an active ingredient which is an organic compound, salts of the active ingredient are investigated in order to improve the solubility, etc., but it is difficult to predict an optimal salt.
In the case of a compound which exhibits crystal polymorphism, the crystal polymorphs are crystal forms which differ in the arrangement of atoms or molecules in the crystal although having the same molecule. The crystal polymorphs differ in the peaks obtained by X-ray powder diffractometry (XRD). It is also known that the crystal polymorphs differ in solubility, stability, peroral absorbability, etc., and it is required for developing medicines to find out a crystal form which is optimal from various standpoints.
At present, a plurality of inhibitors each combine c-Met inhibitory activity and VEGFR2 inhibitory activity have been reported as antitumor agents. As a compound having excellent c-Met/VEGFR2 inhibitory activity and showing antitumor activity, 4-(2-fluoro-4-(3-(2-phenylacetyl)thioureido)phenoxy)-7-methoxy-N-methylquinoline-6-carboxamide (hereinafter referred to also as “compound 1”) has been reported (Patent Documents 1 and 2 and Non-Patent Documents 1 and 2). It has also been reported that compound 1 is useful as a therapeutic agent for osteoporosis (Patent Document 3).